PGC-1α regulates lipid accumulation by coordinating fatty acid synthesis and oxidation in goose fatty liver

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a key regulator of lipid metabolism, particularly in fatty acid oxidation and energy homeostasis. A recent study revealed that PGC-1α exhibits differential expression in mammalian and goose fatty liver, but its function in lipid accumulation in goose fatty liver remains unclear. In this study, thirty 63-day-old male Landes geese were randomly assigned to control and overfeeding groups. Histological analysis was performed using Hematoxylin and Eosin staining and Sirius Red staining after feeding. In vitro, primary goose hepatocytes were treated with lipid accumulation-inducing factors, and PGC-1α mRNA expression was measured. Overexpression and RNA interference of PGC-1α were conducted in primary hepatocytes, followed by transcriptome sequencing analysis. Differential gene expression related to lipid metabolism was analyzed in both goose liver tissue and cultured cells. Our results indicated that despite significant lipid deposition in the liver, no fibrosis was observed in goose fatty liver. PGC-1α mRNA expression was upregulated after glucose, insulin, and palmitic acid treatment (P < 0.05), with no significant changes observed after sodium oleate treatment (P > 0.05). After knocking down PGC-1α, lipid deposition occurred in cells, while overexpression of PGC-1α improved lipid accumulation. Transcriptome sequencing analysis revealed significant upregulation of genes involved in lipid metabolism in PGC-1α-overexpressing cells, particularly in pathways related to arachidonic acid metabolism, fatty acid biosynthesis, linoleic acid metabolism, and adipocytokine signaling. Key genes such as ACSS2, ACOX1, CPT1A, ACSL1 and ACADL were significantly upregulated in both PGC-1α-overexpressing cells and fatty livers from overfed geese (P < 0.05). Knockdown of PGC-1α led to a significant reduction in the mRNA levels of ACSS2, ACOX1, and CPT1A (P < 0.05). In conclusion, these findings demonstrate that PGC-1α activation enhances both fatty acid oxidation and synthesis-related pathways in goose hepatocytes, thereby facilitating lipid turnover and reducing excessive lipid accumulation. This "dual-regulatory" role may represent a unique adaptive mechanism by which geese mitigate hepatic steatosis without triggering inflammation or fibrosis.